Smith-Lemli-Opitz syndrome (SLOS) is a serious dysmorphia and mental retardation condition caused by cholesterol deficiency due to inactivity of the synthetic enzyme 7-dehydrosteroI-delta7-reductase (Dhcr7). Cholesterol in blood and tissues is low, and that of delta7- and delta8-cholesterol high as result of the block. Deficient cholesterol impacts normal embryonic and fetal somatic development resulting in problems of growth, learning, language and behavior. While deficient cholesterol during early development is the cause of CNS abnormalities, the investigators questioned whether neurosteroids could also be clinically important since they can have influence on behavior. Conditions possibly affected by neurosteroids can exhibit cognitive delay, sensory hyperactivity, violent outbursts, destruction, sleep deprivation, and autism. Reduced neurosteroids would also be expected secondary to cholesterol deficiency, as would synthesis of novel delta7 and delta8 neurosteroids, with potentially altered activity. The neurosteroids of primary interest are the modulators of the membrane receptors (MR), GABAA, and NMDA, such as DHEA sulfate, pregnenolone sulfate, and allopregnanolone. These form two groups, steroid sulfates and allopregnanolone, which have opposing interactions with the MRs, and it has been suggested that their balance is neurologically important. Clearly, compromising the homeostasis by introducing components of as yet unknown activity could have behavioral consequences. The investigators plan to use GC/MS to determine delta7 and delta8 neurosteroids in urine and serum of patients with SLOS. Urinary metabolites are likely to be formed largely in ovary and adrenal, with liver catabolism, than to originate in brain. Nevertheless, their presence would indicate that mechanisms for their synthesis are active in SLOS patients. The investigators will also study available Dhcr7 deficiency mouse models with null and missense mutations. Such animals will be used in behavioral and therapeutic studies, for which defining their brain neurosteroid make-up will be a requirement. Further, possible toxic effects of delta7 and delta8 neurosteroids given to normal mice and potential beneficial effects of normal neurosteroids to Dhcr7 mice will be investigated through behavioral studies. In addition, the investigators will see if supplementary cholesterol (labeled) behaviorally improves Dhcr7 deficient mice and is incorporated into brain, as is, or as neuroactive steroid. All studies will require high sensitivity steroid analysis by chemical ionization (CI) GC/MS and HPLC/MS.